The proposed epidemiologic family study will systematically examine the vulnerability to nicotine dependence due to the combined transmission of genes and family/cultural environmental factors (i.e., familial liability). Four areas are addressed in the proposed study: 1.) the familial liability for nicotine dependence associated with different phenotypes or characteristics of nicotine dependence (e.g. also meeting DSM-IV criteria); 2.) the degree of shared familial liability between nicotine dependence and other substance use and mental disorders; 3.) the interaction between familial liability for nicotine dependence and non-familial environmental factors in the etiology of nicotine dependence; 4.) familial liability, non-familial factors, and individual factors that may be partially under genetic control (such as nicotine metabolism) that contribute to estimated differences in nicotine dependence between African Americans and Caucasians, both to spotlight factors that contribute to nicotine dependence in a group at high risk of cancer mortality (African Americans) and to identify protective factors by comparing racial groups with substantially different cigarette smoking profiles. This epidemiologic case - control family study is designed to examine the familial transmission of nicotine dependence among adults 25 to 44 years of age and their families. This age range will be used because the period of risk for daily smoking is largely concluded by age 25 and adults between these ages are still likely to have living parents. Cases will be nicotine dependent by a threshold score of 4 or more on the Fagerstrom Test of Nicotine Dependence (FTND). Controls will be smoking exposed (having smoked at least 100 cigarettes) but never nicotine dependent (FTND = 0). For cases one sibling and both parents will be sought. For controls one sibling will be sought. Direct interviews will be conducted with the case and control family members. The information gathered will include their cigarette smoking, psychiatric disorders, and other substance use, as well as demographic and medical history information. All of the interviewed family members will provide family history of cigarette smoking, substance use and psychiatric disorders. Additionally, cases and controls will be asked about the cigarette smoking, alcohol use and behavior problems of their offspring. This study provides a population-based context for genetic and metabolism studies in the Collaborative Study on the Genetics of Nicotine Dependence. Ascertainment, interviewing, and data management will be integrated across studies. Additionally, as part of the unique opportunity presented by the scientific integration of Projects 1, 2, and 3, we will incorporate genetic, metabolic and epidemiologic measures of a broad array for factors in the development of risk factor models for nicotine dependence.